Hunter syndrome or mucopolysaccharidosis type II is one of the lysosomal storage diseases (LSD) in which mucopolysaccharides such as glycosaminoglycan (GAG) do not decompose to thereby accumulate in lysosomes due to a deficiency of iduronate-2-sulfatase (IDS). GAG accumulates in all cells of the body and causes various symptoms, which include prominent facial features, large head, and abdominal distension due to hypertrophy of the liver or spleen, and are accompanied by hearing loss, heart valve diseases, obstructive respiratory diseases, and sleep apnea. It may also involve a limitation of joint motion as well as nervous system symptoms and developmental delay caused by invasion of the central nervous system. Hunter syndrome is known to occur in about 1 out of 162,000 people and is inherited as an X-linked recessive form, which causes great pains for not only the patients but also their family members.
Up to the present, various methods have been attempted to treat Hunter syndrome, such as bone marrow transplantation, enzyme supplementation, gene therapy, and the like. The bone marrow transplantation has the disadvantages that although the symptom is significantly improved, it is difficult to find a donor whose human leukocyte antigen (HLA) matches with that of the patient and that the mortality rate before and after surgery of the donor whose HLA does not match with that of the patent is high. The gene therapy refers to a method in which a normal IDS gene is injected into the body using a viral or non-viral vector such as an adenovirus or a retrovirus. However, the gene therapy remains at an experimental level and is not yet clinically available.
Currently, the most widely used method is the enzyme replacement therapy (ERT) in which a recombinant IDS enzyme is administered to a patient. Normally, the patient visits the hospital once a week and is administered intravenously by professional medical staff. It takes 3 to 4 hours or longer for a single administration.
Patients suffering from Hunter syndrome have great limitations in everyday life because they have difficulties in catching objects or gait abnormality due to abnormalities of the joint system, or they often have developmental disorders, cognitive disorders, and behavior problems due to nervous system disorders. Therefore, the conventional intravenous infusion therapy, which involves frequent visits to the hospital and long treatment times, may lower the quality of life for the patients and their caregivers. More importantly, there is a problem that the therapeutic effect is significantly reduced due to the lowered compliance of the patents with the medication. Due to the characteristics of the conventional treatment method of supplementing IDS by an intravenous injection once a week, the concentration of IDS in the patient's body was the highest immediately after the intravenous injection, but gradually decreases over time, thereby increasing the concentration of GAG again in the body. An increase in the concentration of GAG leads to severe aggravation of the symptoms. Further, given the high severity and irreversibility of the symptoms of Hunter syndrome in general, if the patient misses the appropriate treatment period, the resulting aggravation of the symptoms can be very fatal and can greatly shorten the patient's life expectancy.
As discussed above, the intravenous administration of IDS in the conventional method for treating Hunter syndrome has the problem that the therapeutic effect is greatly restricted and the life expectancy of the patients can be shortened due to the lowered compliance of the patients with the medication. Therefore, there is a pressing demand for a new formulation and a treatment method to resolve the above-mentioned problem.